|D.L. Gutterman, PharmD, Glaxo Wellcome, Research Triangle, NC, presented the latest safety and efficacy data on Imitrex(R) (sumatriptan). The data were collected from controlled trials on more than 25,000 patients treated for over 140,000 migraine attacks. Inclusion of information from postmarketing surveillance studies increased the number of SUMA-medicated patients to over five million. Many years of experience showed SUMA to be highly effective and the standard for other triptans in research. Careful review of all available data found less than one per million treatments with SUMA led to a cardiovascular-related event. Please consult the accompanying information on Imitrex Tablets and Injection.|
|Background on sumatriptan (SUMA)||
The development of this drug is based on serotonin pharmacology
and migraine headache pathophysiology. Research since the 1950s
identified 3 main families of serotonin (5-HT) receptors
designated as 1, 2, and 3 with many subtypes (A, B, C, etc) in
each family. Sicuteri launched the 5-HT theory of migraine with
the discovery that methysergide (METH), a 5-HT type 2 blocker,
helps relieve migraine (Int Arch Allergy 1959;15:300-307).|
Synthesis of SUMA in the late 1980s corrected the limitations of ergotamine (E) and dihydroergotamine (DHE), both nonspecific 5-HT receptor agonists. As a selective 5-HT type 1 agonist, SUMA does not stimulate other 5-HT receptors which cause nausea, vomiting and diarrhea as seen with METH, E, and DHE. Also, SUMA relieves sensitivity to light, sound, and smell in addition to controlling the nausea and vomiting of migraine.
|Onset of relief||Gutterman found over 80% of SUMA-treated patients responded within two hours of dosing. The speed of effect was 10 minutes after subcutaneous injection, 15 minutes following nasal instillation, and 30 minutes with oral administration.|
|Consistency of response with oral dosing||Data from a well-controlled trial in 1100 migraine patients led Gutterman to conclude that a 50-mg dose of SUMA gave the best balance of efficacy and safety compared with placebo, 25 mg, and 100 mg. Beginning at 30 minutes postdose, the 25-, 50-, and 100-mg tablets provided significantly more pain relief than placebo. The 50- and 100-mg doses proved to be more effective than the 25-mg dose at two hours continuing to the end of the 4-hour observation period. At 4 hours, the percentages of patients reporting pain relief with SUMA were: 100 mg,79%; 50 mg, 78%; 25 mg, 67%; and placebo, 40%.|
|Sumatriptan (SUMA) nasal spray||
Two double-blind, well-controlled clinical studies showed that
a 20-mg instillation led to a 15 minute onset of pain relief.
This dose was effective in 55% to 64% of the patients studied.|
Eighty percent of the patients complained of nausea before using the assigned nasal spray. Two hours after SUMA dosing the reported percentages of patients with nausea were: placebo, 48% and 50%; 10-mg dose,32% and 40%; and 20-mg dose,28% in both studies.
Taste disturbance is the only adverse effect reported with intranasal SUMA. Patients complained of the taste as "bad, bitter, or unpleasant." Single doses provoked this complaint in 19% of the patients taking 10 mg and in 25% after 20 mg. Multiple intranasal doses, taken by 299 patients in a third study, did not increase the percentage of taste complaints.
|Cardiovascular safety with SUMA||
Gutterman found only 17 cardiovascular adverse events in nearly
7000 patients monitored by electrocardiography (ECG):|
Other studies using angiography, positron emission tomography (PET) and SUMA rechallenge support the conclusion that induced cardiovascular events occur as less than one per million doses. According to all available data, the cardiovascular events seen with SUMA are usually mild, early in onset, short-lived, and resolve spontaneously.
|Comments on SUMA||SUMA is remarkably safe and clearly effective in treating acute migraine headache. The intranasal preparation eases the delivery of SUMA and approximates the onset of action noted with the subcutaneous injection. See "New Triptans for Treating Migraine" in this issue of CONRAD NOTES.|
Presented at Thirty-ninth Annual Scientific Meeting, American
Association for the Study of Headache (AASH), June 19-22, 1997
Copyright © 1997 Conrad Group, Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / September 1997